Prenatal opiate exposure in the human neonate is associated with a variable course of stress abstinence in the 2-5 days after birth. Medical management of Neonatal Abstinence Syndrome (NAS) is impaired by problems in predicting the onset, course and severity of NAS. New methods to probe ongoing autonomic stability and global neurodevelopmental function are needed for NAS assessment and treatment. Stress abstinence postnatally may be more harmful to the neonatal brain when repeated cycles of opiate withdrawal in utero occur. To examine prenatal exposure type, methadone treated pregnant women (n=40) from a rural, Caucasian cohort will be interviewed in the third trimester and following birth using quantity-variability-frequency methods for drug, tobacco and alcohol history. Mothers will be grouped based on early (G1, n=20) vs. late entry (G2, n=20) to a Narcotics Treatment Program. Demographically similar infants (G3, n=20) will be compared to exposure groups using algorithms developed in our laboratory to detect the periodicity and bout structure of spontaneous movements (SM) a putative autonomic probe of arousal regulatory integrity. Healthy human neonates express 1-5 minute cycles of 5-25 second bursts of SM. This state-independent, primitive arousal process is coupled to brainstem cardiorespiratory function beginning in the third trimester. Our preliminary studies in apneic and alcohol-exposed infants at high risk for Sudden Infant Death Syndrome (SIDS) revealed reduced vigor in SM burst duration compared to normative samples. Methadone and opiate-exposed infants are similarly high risk (RR= 3-9) for SIDS. A second goal of this study is to examine NAS severity with the SM method in infants that have been exposed to repeated cycles of opiate withdrawal in utero. In the proposed studies, G1 and G2 infants will be compared in two phases of the postnatal adaptation: in Study 1, all infants will be monitored prior to withdrawal (12-24 h after birth) using actigraphy to capture high frequency SM burst structure over the nocturnal phase. In Study 2, the onset, course and severity of NAS withdrawal in G1 and G2 will be compared using the SM method and the Finnegan Score, the standard clinical assessment. Mothers will be carefully screened through clinical interview for drug, tobacco and alcohol history at recruitment in the third trimester and following birth and through prenatal and birth urinary screens and infant meconium. Psychosocial, cognitive and psychological wellbeing, methadone dose, and other medications will be included as covariates or predictors. This project will contribute a new objective method to evaluate: 1.) arousal regulatory and autonomic function of the opiate-exposed infant at birth, and 2.) role of cyclic binge-withdrawal fetal history in the incidence and severity of NAS in methadone-maintained women. Thesaurus Term Arousal regulation, autonomic function, drug abuse, fetus toxicology, methadone, pregnancy, smoking, mother /infant health care, outcomes research, Sudden Infant Death Syndrome, Neonatal Abstinence Syndrome, clinical research, female, human pregnant subject, human subject, infant human (0-1 year) PUBLIC HEALTH RELEVANCE: Opiate addiction and the exposure to methadone and other opiate drugs in utero have created the need to determine both the consequences and the best medical treatment for these infants before and after birth. Opiate exposed infants are at increased risk for Sudden Infant Death Syndrome and this project will study the pattern of prenatal exposure and examine the status of the brain at birth during sleep and while the infant is in opiate withdrawal. The purpose is to identify how SIDS risk develops and develop strategies to protect these vulnerable infants.